Impact of esophageal mucosal permeability markers on provocation-induced esophageal reflexes in high-risk infants

Abstract

Esophageal distal baseline impedance (DBI) is an indicator of mucosal integrity; lower values suggest increased permeability. Aims were to characterize the (1) effect of DBI category (<900 Ω, 900-2000 Ω, and >2000 Ω) on sensory-motor characteristics of mid-esophageal provocation-induced motility reflexes, and (2) clinical outcomes among high-risk human infants evaluated for gastroesophageal reflux disease. Symptomatic infants (N = 49, 41 ± 3 weeks postmenstrual age) underwent pH-impedance testing to characterize acid reflux index (ARI) and DBI, and pharyngo-esophageal manometry to examine upper esophageal sphincter (UES), peristaltic, and lower esophageal sphincter (LES) functions. Sensory-motor response characteristics included response threshold (ml), occurrence (%), latency (s), duration (s), and magnitude (mmHg) upon mid-esophageal stimulations (0.1-2.0 ml of air, water, and apple juice). Motility and clinical outcomes were compared among DBI groups. In infants with DBI <900 Ω and 900-2000 Ω (vs. >2000 Ω): (a) Long-term feeding milestones did not differ (p > 0.05); (b) complete peristaltic propagation decreased in 900-2000 Ω (p < 0.05), polymorphic waveforms increased in <900 Ω and 900-2000 Ω (p < 0.05); (c) media effects were noted with liquids (vs. air) wherein UES and esophageal contractility were prolonged in <900 Ω and 900-2000 Ω (p < 0.05), and esophageal sensitivity heightened for <900 Ω with water and for 900-2000 Ω with air (both p < 0.05). ARI was not correlated with DBI in infants with chronic lung disease (r = 0.05, p = 0.82). We conclude that pharyngo-esophageal motility sensory-motor characteristics in infants are modified by DBI category. These preliminary findings pave-the-way for further physiological testing in convalescing high-risk infants to ascertain potential mechanisms of airway-digestive reflex interactions and symptom generation, which may lead to targeted therapies.

Keywords: distal baseline impedance; esophageal motility; gastroesophageal reflux disease; pH-impedance; prematurity.

FIGURE 1

Oral feeding and breathing outcomes among DBI groups. Comparisons were performed within and between DBI groups, with patient n‐values denoted by numbers inside the bars. There were no significant differences between DBI groups (all p > 0.05). (a) Feeding methods‐ Tube defined as any tube feeding; PO defined as independent oral feeding. Despite the severity of mucosal permeability, majority of infants were achieving full oral feeding at either discharge or 1‐year of age (p < 0.05). Also, note that most of the infants in the <900 Ω and 900–2000 Ω groups improved between evaluation and discharge. (b) Breathing methods‐ Respiratory support defined as nasal cannula oxygen. No support defined as room air. Although there were no distinct differences with maturation or between DBI groups, note that >77% of infants in any DBI group were not on any respiratory support at discharge. Data from DBI <900 Ω (n = 9), DBI 900–2000 Ω (n = 31), and DBI >2000 Ω (n = 9) are shown for evaluation and discharge. However, at 1‐year age, the data includes DBI <900 Ω (n = 8), DBI 900–2000 Ω (n = 29), and DBI >2000 Ω (n = 7).

FIGURE 2

DBI and stimulus media interactions for UES contractile response characteristics. *p < 0.05 versus water, †p < 0.05 versus apple juice, ‡p < 0.05 versus liquid. Note that (a) UES‐contractile response duration occurring with secondary peristalsis is prolonged with air in 900–2000 Ω and <900 Ω DBI groups, indicating increased mechano‐sensitivity, whereas (b) UES‐contractile response occurring after esophago‐deglutition reflex is more in the <900 Ω DBI group with apple juice.

FIGURE 3

DBI and stimulus media interactions for esophageal contractile characteristics. *p < 0.05 versus water, †p < 0.05 versus apple juice, ‡p < 0.05 versus liquid. With DBI <900 Ω, esophageal contraction durations at proximal, middle, and distal esophageal segments between air and liquid were distinct (p < 0.05), suggesting differences in mechano‐ and chemo‐sensitive effects. Note that in the proximal esophagus, the differences were noted with apple juice whereas the middle and distal esophagus had differences in air between the DBI groups.

FIGURE 4

Effects of chronic lung disease (CLD) in infancy on distal baseline impedance (DBI) relationships with esophageal acid exposure. Comparisons were made between CLD and no CLD groups, DBI versus acid reflux index (ARI), and DBI versus longest reflux event. (a) DBI versus ARI relationships: In infants without CLD (n = 24), DBI decreases with ARI increase, whereas there was no correlation of DBI and ARI in infants with CLD (n = 25), or a difference between the two groups, indicating that ARI is the driving variable in the DBI value, not CLD. (b) DBI versus longest reflux duration relationships: In the infants without CLD, DBI decreases with longer events, whereas there was no correlation for the CLD group.